Ring closure Wittig condensation

Aminomethylation of cyclododecanone (79) gave 86a which was converted to 1,2-dimethylenecyclododecane (87) via the Wittig condensation, quaternization, and Hofmann elimination. Bromination of 87 to the ( )-dibromide 88 (98 % yield) was the key step in this approach. The routine synthetic sequence modified the side chains of 88 to provide the ( )-dialdehyde 88b whose McMurry ring closure, followed by removal of the newly formed unsaturated center, completed the synthesis. 

The Wittig-like reactions are well known for C=C bond formation. An intramolecular process can serve as a ring closure and has been generally employed in the synthesis of numerous macrocyclic natural products [150]. Oishi and coworkers [151] applied this strategy to the synthesis of the aglycone (252) of the antibiotics venturicidins A and B. Thus, as shown in Scheme 84, the aldehyde phosphate 250 was subjected to the modified intramolecular Wittig-Homer condensation with a mild base, yielding the macrocycle 251 in 48% yield. 

The same year, Gerlach described a synthesis of optically active 1 from (/ )- ,3-butanediol (7) (Scheme 1.2). The diastereomeric esters produced from (-) camphorsulfonyl chloride and racemic 1,3-butanediol were fractionally recrystallized and then hydrolized to afford enantiomerically pure 7. Tosylation of the primary alcohol, displacement with sodium iodide, and conversion to the phosphonium salt 8 proceeded in 58% yield. Methyl-8-oxo-octanoate (10), the ozonolysis product of the enol ether of cyclooctanone (9), was subjected to Wittig condensation with the dilithio anion of 8 to give 11 as a mixture of olefin isomers in 32% yield. The ratio, initially 68 32 (E-.Z), was easily enriched further to 83 17 (E Z) by photolysis in the presence of diphenyl disulfide. The synthesis was then completed by hydrolysis of the ester to the seco acid, conversion to the 2-thiopyridyl ester, and silver-mediated ring closure to afford 1 (70%). Gerlach s synthesis, while producing the optically active natural product, still did not address the problem posed by the olefin geometry. 

Fried s group at Syntex has described a similar synthesis of zearalenone employing a Wittig condensation and ring closure by intramolecular lactonization (Scheme 1.27). The aromatic residue 131 was constructed from the known ethyl o-orsellinate diacetate (130) by acid hydrolysis and methylation of the phenolic hydroxy groups. 

The condensation of iV-triphenylphosphoraniliden-benzamidine with acyclic a,P-unsaturated aldehydes produces dihydropyrimidines in good to high yields. The reaction mechanism probably involves an aza-Wittig reaction followed by a 6e-n -electrocyclic ring closure of the azatriene intermediate to give dihydropyrimidines, which is oxidized to the corresponding pyrimidines. 

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